Sébastien Barbat-Artigas

Menopause and sarcopenia : A potential role for sex hormones.

Menopause is associated with a decline in estrogen levels, which could lead to an increase in visceral adiposity as well as a decrease in bone density, muscle mass and muscle strength. This decline in muscle mass, known as sarcopenia, is frequently observed in postmenopausal women. Potential causes of sarcopenia include age-related changes in the hormonal status, low levels of physical activity, reduced protein intake and increased oxidative stress. However, the role of sex hormones, specifically estrogens, on the onset of sarcopenia is controversial. Preventing sarcopenia and preserving muscle strength are highly relevant in order to prevent functional impairment and physical disability. To date, resistance training has been shown to be effective in attenuating age-related muscle loss and strength. However, results on the effect of hormonal supplementation to treat or prevent sarcopenia are contradictory. Further research is needed to identify other potential mechanisms of sarcopenia as well as effective interventions for the prevention and treatment of sarcopenia. Therefore, the purpose of this review will be to examine the role of sex hormonal status in the development of sarcopenia. We will also overview the physical as well as metabolic consequences of sarcopenia and the efficiency of different interventions for the prevention and treatment of sarcopenia.

Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans

Mitochondrial dysfunction is implicated in skeletal muscle atrophy and dysfunction with aging, with strong support for an increased mitochondrial‐mediated apoptosis in sedentary rodent models. Whether this applies to aged human muscle is unknown, nor is it clear whether these changes are caused by sedentary behavior. Thus, we examined mitochondrial function [respiration, reactive oxygen species (ROS) emission, and calcium retention capacity (CRC)] in permeabilized myofibers obtained from vastus lateralis muscle biopsies of healthy physically active young (23.7±2.7 yr; mean±sd) and older (71.2±4.9 yr) men. Although mitochondrial ROS and maximal respiratory capacity were unaffected, the acceptor control ratio was reduced by 18% with aging, suggesting mild uncoupling of oxidative phosphorylation. CRC was reduced by 50% with aging, indicating sensitization of the mitochondrial permeability transition pore (mPTP) to apoptosis. Consistent with the mPTP sensitization, older muscles showed a 3‐fold greater fraction of endonuclease G (a mitochondrial proapoptotic factor)‐positive myonuclei. Aged muscles also had lower mitophagic potential, based on a 43% reduction in Parkin to the voltage‐dependent anion channel (VDAC) protein ratio. Collectively, these results show that mitochondrial‐mediated apoptotic signaling is increased in older human muscle and suggest that accumulation of dysfunctional mitochondria with exaggerated apoptotic sensitivity is due to impaired mitophagy.—Gouspillou, G., Sgarioto, N., Kapchinsky, S., Purves‐Smith, F., Norris, B., Pion, C. H., Barbat‐Artigas, S., Lemieux, R, Taivassalo, T., Morais, J. A., Aubertin‐Leheudre, M., Hepple, R. T. Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans. FASEB J. 28, 28–1621 (1633). www.fasebj.org

How to assess functional status: A new muscle quality index

Aging is associated with decreases in muscle mass, muscle strength and muscle power, with muscle strength declining at a higher rate than muscle mass, but at a lower rate than muscle power. This progressive mismatch suggests a deterioration of muscle “quality” that may lead to functional incapacities. Although it may be difficult to synthesize the concept of muscle quality, the aim of the present paper was to propose a clinical definition of muscle quality in regard to the functional status. Accordingly, the muscle strength or muscle power per unit of muscle mass ratios appear to be clinically relevant markers of muscle quality. Several mechanisms susceptible to influence these ratios have been described, among which age, gender, sex hormones, obesity, physical activity and fibrosis. Various methods to assess muscle quality in both the clinical and research fields have also been listed, with a particular interest for the tests used to measure muscle power. Finally, we proposed a clinical screening tool to detect individuals at risk of functional incapacities. Briefly, the muscle quality score is based on handgrip strength assessment by hand dynamometer, muscle mass measurement by bioelectrical analysis, and leg muscle power estimation using a chair stand test.

The Relationship between Muscle Fiber Type-Specific PGC-1α Content and Mitochondrial Content Varies between Rodent Models and Humans

PGC-1α regulates critical processes in muscle physiology, including mitochondrial biogenesis, lipid metabolism and angiogenesis. Furthermore, PGC-1α was suggested as an important regulator of fiber type determination. However, whether a muscle fiber type-specific PGC-1α content exists, whether PGC-1α content relates to basal levels of mitochondrial content, and whether such relationships are preserved between humans and classically used rodent models are all questions that have been either poorly addressed or never investigated. To address these issues, we investigated the fiber type-specific content of PGC-1α and its relationship to basal mitochondrial content in mouse, rat and human muscles using in situ immunolabeling and histochemical methods on muscle serial cross-sections. Whereas type IIa fibers exhibited the highest PGC-1α in all three species, other fiber types displayed a hierarchy of type IIx>I>IIb in mouse, type I = IIx> IIb in rat, and type IIx>I in human. In terms of mitochondrial content, we observed a hierarchy of IIa>IIx>I>IIb in mouse, IIa >I>IIx> IIb in rat, and I>IIa> IIx in human skeletal muscle. We also found in rat skeletal muscle that type I fibers displayed the highest capillarization followed by type IIa >IIx>IIb. Finally, we found in human skeletal muscle that type I fibers display the highest lipid content, followed by type IIa>IIx. Altogether, our results reveal that (i) the fiber type-specific PGC-1α and mitochondrial contents were only matched in mouse, (ii) the patterns of PGC-1α and mitochondrial contents observed in mice and rats do not correspond to that seen in humans in several respects, and (iii) the classical phenotypes thought to be regulated by PGC-1α do not vary exclusively as a function of PGC-1α content in rat and human muscles.

Exploring the Role of Muscle Mass, Obesity, and Age in the Relationship Between Muscle Quality and Physical Function

BACKGROUND Divergent conclusions emerge from the literature regarding the relationship between muscle quality (defined as muscle strength per unit of muscle mass) and physical function. These contrasted results may be due to the influence of factors such as age, obesity, and muscle mass itself. Consequently, the aim of the present study was to explore the role of these factors in the relationship between muscle quality (MQ) and physical function. METHODS Data are from 312 individuals (97 men and 215 women) aged 50 years and older. Body composition (dual energy X-ray absorptiometry) and knee extension strength of the right leg (1 repetition maximum) were assessed. Appendicular lean body mass index (AppLBMI) and MQ (knee extension strength /right leg lean mass) were calculated. A composite score of physical function was created based on the timed up-and-go, alternate step, sit-to-stand, and balance tests. RESULTS MQ was significantly associated with physical function when AppLBMI (β = 0.179; P = .004) and body mass index (BMI) (β = 0.178; P = .003), but not age (β = 0.065; P = .26), were included in regression analysis. AppLBMI (β = 0.221; P < .001), BMI (β = 0.234; P < .001), and age (β = 0.134; P = .018) significantly interacted with MQ to determine physical function. CONCLUSIONS Our results show that muscle mass, obesity, and age influence the relationship between MQ and physical function, suggesting that these factors should be taken into account when interpreting MQ. Even so, higher levels of MQ were associated with higher physical function scores. Nutritional and physical activity interventions may be designed in this regard.

The impact of ageing, physical activity, and pre‐frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in men

The exact impact of ageing on skeletal muscle phenotype and mitochondrial and lipid content remains controversial, probably because physical activity, which greatly influences muscle physiology, is rarely accounted for. The present study was therefore designed to investigate the effects of ageing, physical activity, and pre‐frailty on skeletal muscle phenotype, and mitochondrial and intramyocellular lipid content in men.

Effects of tai chi training in dynapenic and nondynapenic postmenopausal women.

Objective:The purpose of the present study was to investigate the effects of a 12-week tai chi program in type I dynapenic and nondynapenic postmenopausal women. Methods:Sixty-two postmenopausal women were recruited. Body composition, handgrip strength, functional capacities, cardiorespiratory functions (forced expiratory volume in 1 s and oxygen consumption per unit time peak), and quality of life (36-item Short-Form Health Survey) were measured before and after the intervention. Results:Type I dynapenic postmenopausal women showed a significant decrease in body weight (P = 0.004), fat mass percentage (P = 0.02), and skeletal muscle mass (SM; in kilograms; P = 0.02), whereas handgrip strength (in kilograms per SMkg; P = 0.04), functional capacity test scores (P ≤ 0.050), and general health perception (P = 0.01) significantly increased. In nondynapenic postmenopausal women, we observed a significantly decreased waist circumference (P = 0.04) and a significantly increased chair-stand test (P < 0.001) and one-leg stance test (P = 0.04) scores. In addition, significantly lower systolic (P ≤ 0.001) and diastolic (P ≤ 0.005) blood pressures were observed in both groups after the intervention. Finally, type I dynapenic women showed a more pronounced general health perception increase compared with nondynapenic individuals (P = 0.03). Conclusions:Tai chi training improved body composition, muscle strength, functional capacities, and general health perception in postmenopausal women, and this last improvement was more pronounced in type I dynapenic individuals. Therefore, tai chi may be considered as an alternative physical training method in preventing the occurrence of disabilities and frailty in postmenopausal women with type I dynapenia.

Toward a sex-specific relationship between muscle strength and appendicular lean body mass index?

BackgroundIn spite of some dissociation between muscle mass and strength, muscle strength is often used as a proxy to identify individuals with low muscle mass (sarcopenia). Thus, the aim of the present study was to investigate the relationship between muscle strength and the appendicular lean body mass index (app LBMI).MethodsOne hundred and five individuals were recruited. Knee extension and handgrip strength were measured. Body composition was assessed by DXA. App LBMI was calculated as appendicular lean body mass divided by height squared.ResultsAt le level of the entire cohort, both handgrip (r = 0.73; p < 0.001) and knee extension strength (r = 0.57; p < 0.001) were associated with app LBMI. However, in women, knee extension strength (r = 0.32; p < 0.05) but not handgrip strength (r = 0.14; p = 0.35) was associated with app LBMI; while in men, handgrip strength (r = 0.43; p < 0.01) but not knee extension strength (r = 0.27; p = 0.09) was associated with app LBMI.ConclusionsMuscle strength appears to be associated with lean body mass; however, handgrip strength may be preferentially used in men and knee extension strength in women to detect sarcopenic individuals. Future larger studies are now needed to confirm our findings and their clinical relevance.

Mitochondrial energy deficiency leads to hyperproliferation of skeletal muscle mitochondria and enhanced insulin sensitivity

Significance Mitochondrial dysfunction is associated with type II diabetes and metabolic syndrome, but whether it is cause or consequence is debated. By showing that increased mitochondrial respiration can impart glucose tolerance, insulin sensitivity, and resistance to high fat diet (HFD) toxicity, we provide evidence that mitochondria contributes to the etiology of metabolic disease. Inactivation of adenine nucleotide translocator isoform 1 (ANT1) results in proliferation of partially uncoupled muscle mitochondrial respiration, creating a sink for excess calories. Although ANT1-deficient muscle induces expression of Fgf21, FGF21 level is not elevated in blood, and FGF21 and UCP1 mRNAs are not increased in liver or brown adipose tissue (BAT). If increased mitochondrial respiration prevents HFD toxicity, then decreased mitochondrial respiration may contribute to metabolic disease. Diabetes is associated with impaired glucose metabolism in the presence of excess insulin. Glucose and fatty acids provide reducing equivalents to mitochondria to generate energy, and studies have reported mitochondrial dysfunction in type II diabetes patients. If mitochondrial dysfunction can cause diabetes, then we hypothesized that increased mitochondrial metabolism should render animals resistant to diabetes. This was confirmed in mice in which the heart–muscle–brain adenine nucleotide translocator isoform 1 (ANT1) was inactivated. ANT1-deficient animals are insulin-hypersensitive, glucose-tolerant, and resistant to high fat diet (HFD)-induced toxicity. In ANT1-deficient skeletal muscle, mitochondrial gene expression is induced in association with the hyperproliferation of mitochondria. The ANT1-deficient muscle mitochondria produce excess reactive oxygen species (ROS) and are partially uncoupled. Hence, the muscle respiration under nonphosphorylating conditions is increased. Muscle transcriptome analysis revealed the induction of mitochondrial biogenesis, down-regulation of diabetes-related genes, and increased expression of the genes encoding the myokines FGF21 and GDF15. However, FGF21 was not elevated in serum, and FGF21 and UCP1 mRNAs were not induced in liver or brown adipose tissue (BAT). Hence, increased oxidation of dietary-reducing equivalents by elevated muscle mitochondrial respiration appears to be the mechanism by which ANT1-deficient mice prevent diabetes, demonstrating that the rate of mitochondrial oxidation of calories is important in the etiology of metabolic disease.

Relationship between different protein intake recommendations with muscle mass and muscle strength

Abstract Objective The purpose of the present study was to examine the relationship between two different levels of protein intake (0.8 vs.1.2 g/kg body weight/day) with muscle mass and muscle strength. Method Seventy-two postmenopausal women were recruited. Body composition (bioelectrical impedance analysis), muscle strength (dynamometer), energy metabolism (indirect calorimetry) and dietary intake (dietary journal) were measured. We divided the women into two groups. Women with a protein intake of ≥ 1.2 g/kg body weight/day were placed in the Protein ≥ 1.2 group (n = 35), whereas women with a protein intake of 0.8–1.19 g/kg body weight/day were categorized in the Protein 0.8–1.19 group (n = 32). Results No significant difference was observed between groups for age, height, skeletal muscle mass, resting energy expenditure, total energy expenditure, carbohydrate and lipid intake. Significant differences between groups were observed for body mass index (p < 0.001), fat mass (p < 0.001) and muscle strength (hand grip and knee extensors) (p < 0.001). More specifically, the Protein ≥ 1.2 group presented a higher muscle strength as well as a lower body mass index and fat mass compared to the Protein 0.8–1.19 group. In addition, the group with a protein intake of ≥ 1.2 g/kg body weight/day presented significantly higher energy intake (p = 0.002), and essential (p < 0.001) and non-essential (p < 0.001) amino acid intake. Interestingly, when muscle strength was adjusted for essential or non-essential amino acids, differences in muscle strength persisted. Conclusion The present study indicates higher levels of muscle strength in postmenopausal women with a protein intake of ≥ 1.2 g/kg body weight/day compared to 0.8–1.19 g/kg body weight/day despite no differences in muscle mass.